Scientific Reports (Jul 2017)

Correlative cellular ptychography with functionalized nanoparticles at the Fe L-edge

  • Marcus Gallagher-Jones,
  • Carlos Sato Baraldi Dias,
  • Alan Pryor,
  • Karim Bouchmella,
  • Lingrong Zhao,
  • Yuan Hung Lo,
  • Mateus Borba Cardoso,
  • David Shapiro,
  • Jose Rodriguez,
  • Jianwei Miao

DOI
https://doi.org/10.1038/s41598-017-04784-5
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 10

Abstract

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Abstract Precise localization of nanoparticles within a cell is crucial to the understanding of cell-particle interactions and has broad applications in nanomedicine. Here, we report a proof-of-principle experiment for imaging individual functionalized nanoparticles within a mammalian cell by correlative microscopy. Using a chemically-fixed HeLa cell labeled with fluorescent core-shell nanoparticles as a model system, we implemented a graphene-oxide layer as a substrate to significantly reduce background scattering. We identified cellular features of interest by fluorescence microscopy, followed by scanning transmission X-ray tomography to localize the particles in 3D, and ptychographic coherent diffractive imaging of the fine features in the region at high resolution. By tuning the X-ray energy to the Fe L-edge, we demonstrated sensitive detection of nanoparticles composed of a 22 nm magnetic Fe3O4 core encased by a 25-nm-thick fluorescent silica (SiO2) shell. These fluorescent core-shell nanoparticles act as landmarks and offer clarity in a cellular context. Our correlative microscopy results confirmed a subset of particles to be fully internalized, and high-contrast ptychographic images showed two oxidation states of individual nanoparticles with a resolution of ~16.5 nm. The ability to precisely localize individual fluorescent nanoparticles within mammalian cells will expand our understanding of the structure/function relationships for functionalized nanoparticles.